HPN (gene) explained

Serine protease hepsin is an enzyme that in humans is encoded by the HPN gene.^{[1] [2]}

Function

Hepsin is a cell surface serine protease.^[3]

Hepson contains a peptidase S1 domain and an SRCR domain. The SRCR domain is located in the extracellular part of the protein, it is formed primarily by three elements of regular secondary structure: a 12-residue alpha helix, a twisted five-stranded antiparallel beta sheet, and a second, two-stranded, antiparallel sheet. The two beta-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate.^[4]

Clinical significance

Hepsin expression is unregulated in prostate cancer and correlates with disease progression.^[5]

Further reading

• Wu Q . Gene targeting in hemostasis. Hepsin . Frontiers in Bioscience . 6 . 3. D192-200 . Feb 2001 . 11171558 . 10.2741/a604.
• Tsuji A, Torres-Rosado A, Arai T, Le Beau MM, Lemons RS, Chou SH, Kurachi K . Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization . The Journal of Biological Chemistry . 266 . 25 . 16948–53 . Sep 1991 . 10.1016/S0021-9258(18)55395-3 . 1885621 . free .
• Kazama Y, Hamamoto T, Foster DC, Kisiel W . Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation . The Journal of Biological Chemistry . 270 . 1 . 66–72 . Jan 1995 . 7814421 . 10.1074/jbc.270.1.66 . free .
• Torres-Rosado A, O'Shea KS, Tsuji A, Chou SH, Kurachi K . Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth . Proceedings of the National Academy of Sciences of the United States of America . 90 . 15 . 7181–5 . Aug 1993 . 8346233 . 47100 . 10.1073/pnas.90.15.7181 . 1993PNAS...90.7181T . free .
• Chen Z, Fan Z, McNeal JE, Nolley R, Caldwell MC, Mahadevappa M, Zhang Z, Warrington JA, Stamey TA . Hepsin and maspin are inversely expressed in laser capture microdissectioned prostate cancer . The Journal of Urology . 169 . 4 . 1316–9 . Apr 2003 . 12629351 . 10.1097/01.ju.0000050648.40164.0d .
• Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA . The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain . Structure . 11 . 9 . 1123–31 . Sep 2003 . 12962630 . 10.1016/S0969-2126(03)00148-5 . free .
• Kirchhofer D, Peek M, Lipari MT, Billeci K, Fan B, Moran P . Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2 . FEBS Letters . 579 . 9 . 1945–50 . Mar 2005 . 15792801 . 10.1016/j.febslet.2005.01.085 . 46441979 . free .
• Pal P, Xi H, Kaushal R, Sun G, Jin CH, Jin L, Suarez BK, Catalona WJ, Deka R . Variants in the HEPSIN gene are associated with prostate cancer in men of European origin . Human Genetics . 120 . 2 . 187–92 . Sep 2006 . 16783571 . 10.1007/s00439-006-0204-3 . 13411333 .
• Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D . Pro-urokinase-type plasminogen activator is a substrate for hepsin . The Journal of Biological Chemistry . 281 . 41 . 30439–46 . Oct 2006 . 16908524 . 10.1074/jbc.M605440200 . free .
• Betsunoh H, Mukai S, Akiyama Y, Fukushima T, Minamiguchi N, Hasui Y, Osada Y, Kataoka H . Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma . Cancer Science . 98 . 4 . 491–8 . Apr 2007 . 17309599 . 10.1111/j.1349-7006.2007.00412.x . 26220332 . 11160002 .

Notes and References

1. Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW . A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells . Biochemistry . 27 . 3 . 1067–74 . Feb 1988 . 2835076 . 10.1021/bi00403a032 .
2. Web site: Entrez Gene: HPN hepsin (transmembrane protease, serine 1).
3. Web site: Entrez Gene: HPN hepsin (transmembrane protease, serine 1).
4. Somoza JR, Ho JD, Luong C, Ghate M, Sprengeler PA, Mortara K, Shrader WD, Sperandio D, Chan H, McGrath ME, Katz BA . The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain . Structure . 11 . 9 . 1123–31 . Sep 2003 . 12962630 . 10.1016/S0969-2126(03)00148-5 . free .
5. Wu Q, Parry G . Hepsin and prostate cancer . Frontiers in Bioscience . 12 . 12. 5052–9 . 2007 . 17569629 . 10.2741/2447 . free .